Publications by authors named "Chongqi Tu"

120 Publications

Multiple Pulmonary Metastases of Recurrent Giant Cell Tumor of Bone with Expression of VEGFR-2 Successfully Controlled by Denosumab and Apatinib: A Case Report and Literature Review.

Cancer Manag Res 2021 3;13:4447-4454. Epub 2021 Jun 3.

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People's Republic of China.

Giant cell tumor of bone (GCTB) is a rare, benign, but locally aggressive bone tumor. It has a high tendency for local recurrence, which may increase the incidence of lung metastasis. Currently, an optimal treatment strategy has not been established because of the rarity of pulmonary metastatic GCTB. Denosumab is the preferred regimen for unresectable metastatic lesions; however, there are no alternative treatment options when patients are resistant to denosumab. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively competes for the vascular endothelial growth factor receptor 2 (VEGFR-2) ATP binding site, and several studies have analyzed the effectiveness of apatinib in advanced or metastatic tumors. However, there is no report of apatinib as an anti-angiogenesis therapy for pulmonary metastatic GCTB to date. Here, we present a case of a 26-year-old female who was diagnosed with recurrent and pulmonary metastatic GCTB. Immunohistochemical (IHC) staining indicated that the tumor cells were positive for VEGFR-2. Denosumab was administered to control the metastases; nevertheless, disease progression was confirmed after four months of treatment. Given the IHC results and rapid disease progression, apatinib was added to the treatment strategy. After 42 months of treatment, the patient showed noticeable symptomatic improvement and considerable tumor shrinkage.
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http://dx.doi.org/10.2147/CMAR.S312846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184137PMC
June 2021

Three-dimensional-printed custom-made hemipelvic endoprosthesis for the revision of the aseptic loosening and fracture of modular hemipelvic endoprosthesis: a pilot study.

BMC Surg 2021 May 26;21(1):262. Epub 2021 May 26.

Department of Orthopaedics, Orthopaedic Research Institute, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, People's Republic of China.

Background: The aims of this pilot study were (1) to assess the efficacy of 3D-printed custom-made hemipelvic endoprosthesis in restoring the natural location of acetabulum for normal bodyweight transmission; (2) to evaluate the short-term function of the revision with this endoprosthesis and (3) to identify short-term complications associated with the use of this endoprosthesis.

Methods: Between February 2017 and December 2017, seven patients received revision with 3D-printed custom-made hemipelvic endoprosthesis. The body weight moment arm (BWMA) and cup height discrepancy (CHD) after primary and revisional surgery were analyzed to assess acetabulum location with plain radiography. After a median follow-up duration of 29 months (range 24-34), the function was evaluated with the Musculoskeletal Tumor Society (MSTS-93) score and Harris hip score (HHS). Complications were recorded by chart review.

Results: The acetabulum locations were deemed reasonable, as evaluated by median BWMA (primary vs. revision, 10 cm vs. 10 cm) and median CHD (primary vs. revision, 10 mm vs. 8 mm). The median MSTS-93 score and HHS score were 21 (range 18-23) and 78 (range 75-82) after the revision. No short or mid-term complication was observed in the follow-up of this series.

Conclusions: Revision with 3D-printed custom-made hemipelvic endoprostheses benefited in reconstructing stable pelvic ring and natural bodyweight transmission for patients encountering the aseptic loosening and fracture of modular hemipelvic endoprosthesis. The revision surgery and appropriate rehabilitation program improved patients' function to a median MSTS score of 22 and pain-free ambulation. The incidence of the complications was low via this individualized workflow.
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http://dx.doi.org/10.1186/s12893-021-01257-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157625PMC
May 2021

Three-dimensional-printed customized prosthesis for pubic defect: clinical outcomes in 5 cases at a mean follow-up of 24 months.

BMC Musculoskelet Disord 2021 Apr 30;22(1):405. Epub 2021 Apr 30.

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, No. 37 Guoxuexiang, 610041, Chengdu, Sichuan, People's Republic of China.

Background: Pubic defects resulting from type III hemipelvectomy are commonly not reconstructed due to the need to preserve the weight-bearing axis. However, the opening of the anterior pelvic ring will inevitably lead to increased pelvic instability. To improve long-term pelvic stability, three-dimensional (3D)-printed customized prostheses were designed to reconstruct pubic defects. This study presents and evaluates the short-term clinical outcomes and complications from the use of this construct.

Methods: Five patients who underwent type III hemipelvectomy and 3D-printed customized prosthesis reconstruction at our institution between 2017 and 2019 were retrospectively analysed. Operation time and blood loss during the operation were recorded. Local and functional recovery was assessed. Prosthetic position and osseointegration were evaluated. Oncology results and complications were recorded.

Results: The prostheses consisted of three with stems and two without. The mean follow-up time was 23.6 months. At the last follow-up, all five patients were alive with no evidence of disease. No deep infections or local recurrence had occurred. The mean blood loss and mean intraoperative time were 1680 ml and 294 min, respectively. The mean functional MSTS score at the final follow-up was 29.8. Fretting wear around the prosthetic stem was found in 3 patients, while bone wear on the normal-side pubis was found in 2 patients. Osseointegration was observed in all patients.

Conclusions: 3D-printed customized prostheses for reconstructing pubic bone defects after type III hemipelvectomy showed acceptable early outcomes. The good outcomes were inseparable from the precision prosthesis design, strict surgical procedures, and sensible postoperative management.
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http://dx.doi.org/10.1186/s12891-021-04294-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091684PMC
April 2021

Pelvic Reconstruction With a Novel Three-Dimensional-Printed, Multimodality Imaging Based Endoprosthesis Following Enneking Type I + IV Resection.

Front Oncol 2021 13;11:629582. Epub 2021 Apr 13.

West China School of Medicine/West China Hospital, Sichuan University, Chengdu, China.

Background And Purpose: Pelvic tumor involving Type I + IV resections are technically challenging, along with various reconstructions methods presenting unsatisfactory outcomes and high complication rates. Since predominating studies preferred adopting pedicle screw-rod system (PRSS) to address this issue, we designed a novel three-dimensional-printed, multimodality imaging (3DMMI) based endoprosthesis with patient-specific instrument (PSI) assistance to facilitate the surgical reconstruction of pelvic tumor involving Enneking Type I + IV resection. We aimed to investigate the clinical effectiveness of this novel endoprosthesis and compare it with PRSS in Type I + IV reconstruction.

Methods: We retrospective studied 28 patients for a median follow-up of 47 months (range, 10 to 128 months) in this study with either 3D-printed endoprosthesis reconstruction (n = 10) or PRSS reconstruction (n = 18) between January 2000 and December 2017. Preoperative 3DMMI technique was used for tumor evaluation, PSI design, virtual surgery, and endoprosthesis fabrication. Clinical, oncological outcomes, functional assessments, and complications were analyzed between the two groups.

Results: Minor surgical trauma with mean operative duration of 251 ± 52.16 minutes (p = 0.034) and median intraoperative hemorrhage of 2000ml (range, 1600, 4000ml) (p = 0.032) was observed in endoprosthesis group. Wide margins were achieved in 9 patients of the endoprosthesis group compared with 10 in the PRSS group (p = 0.09). The 1993 version of the Musculoskeletal Tumor Society score (MSTS-93) was 23.9 ± 3.76 in endoprosthesis group, which was higher than PRSS group (p = 0.012). No statistical significance was found in relapse between two groups (p = 0.36). Complications were observed in two patients in endoprosthesis group compared with 12 patients in PRSS group (p = 0.046).

Conclusion: The novel design of this 3D-printed endoprosthesis, together with 3DMMI and PSI assisted, is technically accessible with favorable clinical outcomes compared with PRSS. Further study is essential to identify its long-term outcomes.
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http://dx.doi.org/10.3389/fonc.2021.629582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078592PMC
April 2021

Three-dimensional-printed porous implant combined with autograft reconstruction for giant cell tumor in proximal tibia.

J Orthop Surg Res 2021 Apr 29;16(1):286. Epub 2021 Apr 29.

Department of Orthopedics, Orthopedic Research Institute, West China Hospital, Sichuan University, No. 37 Guoxuexiang, Chengdu, 610041, Sichuan, People's Republic of China.

Background: This study is to describe the design and surgical techniques of three- dimensional-printed porous implants for proximal giant cell tumors of bone and evaluate the short-term clinical outcomes.

Methods: From December 2016 to April 2020, 8 patients with giant cell tumor of bone in the proximal tibia underwent intralesional curettage of the tumor and reconstruction with bone grafting and three-dimensional-printed porous implant. Detailed anatomy data were measured, including the size of lesion and thickness of the subchondral bone. Prostheses were custom-made for each patient by our team. All patients were evaluated regularly and short-term clinical outcomes were recorded.

Results: The mean follow-up period was 26 months. According to the different defect sizes, the mean size of the plate and mean length of strut were 35 × 35 mm and 20 mm, respectively. The mean affected subchondral bone percentage was 31.5%. The average preoperative and postoperative thickness of the subchondral bone was 2.1 mm and 11.1 mm, respectively. There was no wound infection, skin necrosis, peroneal nerve injury, or other surgical related complications. No degeneration of the knee joint was found. Osseointegration was observed in all patients. The MSTS improved from an average of 12 preoperatively to 28 postoperatively.

Conclusion: The application of three-dimensional-printed printed porous prosthesis combined autograft could supply enough mechanical support and enhance bone ingrowth. The design and operation management lead to satisfactory subchondral bone reconstruction.
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http://dx.doi.org/10.1186/s13018-021-02446-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082833PMC
April 2021

Prolonged balloon occlusion of the lower abdominal aorta during pelvic or sacral tumor resection.

Ann Transl Med 2021 Mar;9(5):416

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China.

Background: To explore the efficacy of lower abdominal aorta balloon occlusion technology in pelvis and sacral tumor surgery and to assess the safety of prolonged balloon occlusion.

Methods: From January 2008 to January 2017, 81 patients were diagnosed with sacrum or pelvic tumor and underwent surgery in our institution. Balloon catheters were placed through the femoral artery to occlude the abdominal aorta of the pelvic tumor and sacrum region undergoing tumor resection. These patients were divided into two group based on single balloon blocking time. Group A had a balloon blocking time of 60 minutes or less, and group B had a balloon occlusion time greater than 60 minutes. The patients in the two groups were compared with regards to operation time, intraoperative blood loss, blood transfusion volume, average length of hospital stay, and postoperative complications.

Results: No balloon displacement or leakage of the abdominal aorta occurred during the operations. The difference in operation time between the two groups was statistically significant (P≤0.05), and the differences in intraoperative blood loss, blood transfusion volume, and average hospital stay between groups A and B were not significant (P>0.05). The incidence of postoperative complications was 12% in group A, and 22.6% in group B, with no statistically significant differences (P>0.05).

Conclusions: Prolonged balloon occlusion was safe and effective in the surgical treatment of complicated pelvic and sacral tumors. It did not increase the incidence of postoperative complications such as distal limb paralysis, arterial thrombosis, or ischemic necrosis.
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http://dx.doi.org/10.21037/atm-21-138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033300PMC
March 2021

Outcomes of Oral Vinorelbine in Progressive Desmoid Fibromatosis-Letter.

Clin Cancer Res 2021 Apr;27(7):2119

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China.

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http://dx.doi.org/10.1158/1078-0432.CCR-20-4755DOI Listing
April 2021

Remarkable response to anti-PD1 immunotherapy in refractory metastatic high-grade myxofibrosarcoma patient: A case report.

Medicine (Baltimore) 2021 Mar;100(12):e25262

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, P. R. China.

Introduction: Myxofibrosarcoma (MFS) is a locally aggressive tumor and has the potential to be fatal because of distant metastasis. Immunotherapy targeting either programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) has recently shown a curative effect on multiple cancers including melanoma, non-small cell lung cancer, and renal cell carcinoma. Although the immunotherapy has been applied in sarcoma, there is little information about the efficiency to treat metastatic MFS.

Patient Concerns: A 42-year-old male presented to the clinic with a mass in the left thigh. Mass resection and ligament replacement surgery were performed.

Diagnoses: The patient was diagnosed as high-grade MFS (federation nationale des centres de lutte contre le cancer, Grade 3) with pulmonary metastasis.

Interventions: In the past few years, he was treated with surgery, chemoradiotherapy, and Anlotinib (an angiogenesis inhibitor), but the metastatic lesion continued to progress. About 40% to 50% of tumor cells in his pulmonary tissues were showed positive PD-L1 expression and his tumor mutational burden was 215Muts. Thus, he received Camrelizumab (PD-1 inhibitor).

Outcomes: Six months after the initiating immunotherapy of Camrelizumab, the size of pulmonary lesions showed marked shrinkage, indicating a partial response. After a follow-up of 18 months, the patient remained in good condition without progressive disease.

Conclusion: This case described here demonstrated that immunotherapy of PD-1 inhibitor is a promising treatment option for refractory MFS with PD-L1 positive or tumor mutational burden -high, which could contribute to effective tumor response.
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http://dx.doi.org/10.1097/MD.0000000000025262DOI Listing
March 2021

ASO Author Reflections: Patient-Derived Tumor Xenografts and Ex Vivo Models Mimic the Clinical Response of Locally Aggressive Tumors to Approved Drug Candidates.

Ann Surg Oncol 2021 Mar 18. Epub 2021 Mar 18.

Department of Orthopeadics, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1245/s10434-021-09840-zDOI Listing
March 2021

Long-term results of uncemented allograft prosthesis composite reconstruction for the tumor in proximal femur: a minimum follow-up of sixty-five months.

BMC Musculoskelet Disord 2021 Feb 1;22(1):128. Epub 2021 Feb 1.

Department of Orthopedic Surgery, West China Hospital of Sichuan University, Guoxue Road 37#, Chengdu, 610041, China.

Background: Uncemented allograft prosthesis composite (APC) has been applied for tumorous bone defect reconstruction in the proximal femur. However, the long-term results are rarely reported. This study aimed to evaluate long-term outcomes of uncemented APC.

Methods: Eighteen patients who received uncemented APC reconstruction in the proximal femur after tumor resections were retrospectively reviewed.

Results: The average resection length was 110 mm (80-154) and the average follow-up was 106.7 months (65-141). Bone union achieved in all patients with an average duration of 7.6 months (5-10). The average HHS, MSTS score and gluteus medius strength at one-year follow-up were 88.0 (80-94), 25.2 (22-28) and 4 (3-5), respectively. While at the last follow-up, the HHS, MSTS score and gluteus medius strength were 83.0 (48-100), 24.0 (10-30) and 4 (2-5), respectively. Five intraoperative fractures were fixed with cerclage wires. Two postoperative periprosthetic and prosthetic fractures received a revision. Three local recurrent patients received a secondary surgery. One of these three lung metastatic patients underwent lung metastatic tumor resection. Another two patients were diagnosed with both bone and lung metastases, only one of them underwent amputation. Two greater trochanteric fractures received no treatment. There were10 severe, 3 moderate and 5 mild allograft resorptions without treatment.

Conclusion: Uncemented APC is a reliable reconstruction for neoplastic bone defect of the proximal femur, especially for the young patient who expected long-life expectancy and good function. Though allograft resorption and trochanteric fracture are the common complications, they seem no effect on the function.
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http://dx.doi.org/10.1186/s12891-021-03991-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849157PMC
February 2021

Case Report: Primary Ewing Sarcoma of the Penis With Multiple Metastases.

Front Pediatr 2020 7;8:591257. Epub 2021 Jan 7.

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China.

Ewing sarcoma is the second most common malignant bone tumor in children, but it rarely originates from extra-skeletal sites. The commonly involved sites of soft tissue include paravertebral spaces, lower extremities, the pelvis, head, and neck, while primary extra-skeletal Ewing sarcoma (EES) located in the genitals is extremely rare. We report a young patient who presented to our hospital with a painful erection of the penis and limited motion of the left hip. Magnetic resonance imaging showed a hyperintense mass with invasion of adjacent tissue in the penis and a heterogeneously high signal lesion in the left proximal femur. F-fluorodeoxyglucose positron-emission tomography detected widespread metastatic lesions in the bilateral lung and multiple skeletons. An incisional biopsy of the penis was performed; the histopathological findings and EWS gene translocation identified by molecular analysis confirmed the diagnosis of Ewing sarcoma. Subsequently, the punch-biopsy specimen from the left femur showed undifferentiated small round cells, a finding consistent with the microscopic presence of Ewing sarcoma metastasis. However, after the first course of multiagent chemotherapy, the penile mass did not obtain stabilization but instead grew progressively with surface ulceration and multidrug resistant bacteria infection. Despite receiving antibiotics and maximal supportive therapy, the patient died from sepsis and lung metastasis complications in the intensive care unit 2 months later. This case indicates that although EES as a subtype of Ewing sarcoma is rare, it can occur virtually in any soft tissue site, even in the genitals. Therefore, clinicians need to distinguish this entity from other soft tissue sarcomas with rapid progression since early diagnosis and timely treatment of EES are pivotal for a favorable prognosis.
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http://dx.doi.org/10.3389/fped.2020.591257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817810PMC
January 2021

Stereolithography-Based Additive Manufacturing of High-Performance Osteoinductive Calcium Phosphate Ceramics by a Digital Light-Processing System.

ACS Biomater Sci Eng 2020 03 20;6(3):1787-1797. Epub 2020 Feb 20.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.

Digital light processing (DLP) is one of the additive manufacturing (AM) technologies suitable for preparation of high-performance ceramics. The present study provided an optimized formula to fabricate osteoinductive calcium phosphate (CaP) ceramics with high precision and controllable three-dimensional (3D) structure. Among the four surfactants, monoalcohol ethoxylate phosphate was the best one to modify the CaP powders for preparing the photocurable slurry with high solid loading and good spreading ability. By testing the photopolymerization property of the 60 wt % solid loading slurry, the appropriate processing parameters including the slice thickness (50 μm), exposure intensity (10.14 mW/cm), and exposure time (8 s) were set to perform the 3D printing of the ceramic green body in the DLP system. After the debinding and sintering, the final CaP ceramics were acquired. The stereomicroscope and SEM observation confirmed the high precision of the ceramics. The average compressive strength of the ceramics with 64.5% porosity reached 9.03 MPa. On only soaking in simulated body fluid for 1 day, an even layer of apatite formed on the ceramic surface. The cell culture confirmed that the ceramics could allow the good attachment, growth, and proliferation of murine bone marrow mesenchymal stem cells. After implantation into the dorsal muscles of beagle dogs for 3 months, abundant blood vessels and obvious ectopic bone formation were observed clearly by the histological evaluation. Therefore, with good bioactivity and osteoinductivity as well as high precision and adjustable mechanical strength, the 3D printed CaP ceramics in the DLP system could have good potential in customized bone-repairing applications.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01663DOI Listing
March 2020

Efficacy and safety of apatinib for patients with advanced extremity desmoid fibromatosis: a retrospective study.

J Cancer Res Clin Oncol 2021 Jul 15;147(7):2127-2135. Epub 2021 Jan 15.

Department of Orthopedics, West China Hospital, Sichuan University, Guoxue Xiang No. 37, Chengdu, 610041, Sichuan, People's Republic of China.

Purpose: Desmoid fibromatosis (DF) is a locally aggressive connective-tissue tumor arising in deep soft tissues. Although multiple therapeutic modalities have been demonstrated effective for DF, there is no standard systemic treatment for progressive and recurrent DF. As a part of systemic treatment, tyrosine kinase inhibitors have shown promising activity against DF with tolerable toxicity profiles. Thus, the aim of this study was to investigate the efficacy and safety of apatinib, a novel multi-target angiogenesis inhibitor, in patients with DF.

Methods: We retrospectively analyzed the medical records of patients with advanced extremity DF regularly treated with apatinib between October 2017 and January 2020 in our center. Apatinib was initially administered with a dose of 250 mg daily and the dose was adjusted according to the toxicity. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors 1.1 criteria. The primary endpoint was progression-free survival (PFS); objective response rates and drug-related adverse events were also evaluated.

Results: A total of 22 (6 male, 16 female) patients with advanced extremity DF were included. The mean medication time was 17 months. None of the patients reached a complete response, but ten (45.5%) patients achieved partial response, and 11 patients (50%) achieved stable disease. One (4.5%) patient developed progressive disease, and the 1-year PFS rate was 95.2%. The disease control rate was 95.4% (21/22) and the objective response rate was 45.5% (10/22). Meanwhile, 18 (81.8%) patients with a tumor shrinkage were accompanied by a decreased signal intensity of lesions in T2-weighted magnetic resonance imaging. The most frequent adverse events included hand-foot syndrome (n = 7, 31.8%), fatigue (n = 6, 27.2%), local pain (n = 4, 18.1%), diarrhea (n = 4, 18.1%).

Conclusion: Apatinib is an effective and well-tolerated option for patients with advanced extremity DF. Indeed, further prospective, randomized studies with larger cases are required to fully explore the clinical utility of apatinib in DF.
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http://dx.doi.org/10.1007/s00432-020-03498-yDOI Listing
July 2021

ASO Author Reflections: Perioperative Targeting of the Pre-metastatic Niche Reduces Metastatic Risk After Resection of Solid Tumors.

Ann Surg Oncol 2021 Jul 5;28(7):4049-4050. Epub 2021 Jan 5.

Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

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http://dx.doi.org/10.1245/s10434-020-09418-1DOI Listing
July 2021

Targeting Myeloid-Derived Suppressor Cells for Premetastatic Niche Disruption After Tumor Resection.

Ann Surg Oncol 2021 Jul 30;28(7):4030-4048. Epub 2020 Nov 30.

Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Surgical resection is a common therapeutic option for primary solid tumors. However, high cancer recurrence and metastatic rates after resection are the main cause of cancer related mortalities. This implies the existence of a "fertile soil" following surgery that facilitates colonization by circulating cancer cells. Myeloid-derived suppressor cells (MDSCs) are essential for premetastatic niche formation, and may persist in distant organs for up to 2 weeks after surgery. These postsurgical persistent lung MDSCs exhibit stronger immunosuppression compared with presurgical MDSCs, suggesting that surgery enhances MDSC function. Surgical stress and trauma trigger the secretion of systemic inflammatory cytokines, which enhance MDSC mobilization and proliferation. Additionally, damage associated molecular patterns (DAMPs) directly activate MDSCs through pattern recognition receptor-mediated signals. Surgery also increases vascular permeability, induces an increase in lysyl oxidase and extracellular matrix remodeling in lungs, that enhances MDSC mobilization. Postsurgical therapies that inhibit the induction of premetastatic niches by MDSCs promote the long-term survival of patients. Cyclooxygenase-2 inhibitors and β-blockade, or their combination, may minimize the impact of surgical stress on MDSCs. Anti-DAMPs and associated inflammatory signaling inhibitors also are potential therapies. Existing therapies under tumor-bearing conditions, such as MDSCs depletion with low-dose chemotherapy or tyrosine kinase inhibitors, MDSCs differentiation using all-trans retinoic acid, and STAT3 inhibition merit clinical evaluation during the perioperative period. In addition, combining low-dose epigenetic drugs with chemokine receptors, reversing immunosuppression through the Enhanced Recovery After Surgery protocol, repairing vascular leakage, or inhibiting extracellular matrix remodeling also may enhance the long-term survival of curative resection patients.
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http://dx.doi.org/10.1245/s10434-020-09371-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703739PMC
July 2021

The morphological effect of nanostructured hydroxyapatite coatings on the osteoinduction and osteogenic capacity of porous titanium.

Nanoscale 2020 Dec 26;12(47):24085-24099. Epub 2020 Nov 26.

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China.

Weak osteogenic activity affects the long-term fixation and lifespan of titanium (Ti) implants. Surface modification along with a built-in porous structure is a highly considerable approach to improve the osteoinduction and osseointegration capacity of Ti. Herein, the osteoinduction and osteogenic activities of electrochemically deposited (ED) nanoplate-like, nanorod-like and nanoneedle-like hydroxyapatite (HA) coatings (named EDHA-P, EDHA-R, and EDHA-N, respectively) were evaluated in vitro and in vivo by comparison with those of acid/alkali (AA) treatment. The results revealed that the apatite forming ability of all nanostructured EDHA coatings was excellent, and only 12 h of soaking in SBF was needed to induce a complete layer of apatite. More serum proteins adsorbed on EDHA-P than others. In cellular experiments, different from those on EDHA-R and EDHA-N, the cells on EDHA-P presented a polygonal shape with lamellipodia extension, and thus exhibited a relatively larger spreading area. Furthermore, EDHA-P was more favorable for the enhancement of the proliferation and ALP activity of BMSCs, and the up-regulation of OPN gene expression. Based on the good biological performance in vitro, EDHA-P was selected to further evaluate its osteoinduction and osteogenic activities in vivo by comparison with AA treatment. Interestingly, a greater ability of ectopic osteoinduction was observed in the EDHA-P group compared to that in the AA group. At the osseous site, EDHA-P promoted more bone on/ingrowth, and had a higher area percentage of newly formed bone in the bone-implant interface and inner pores of the implants than in the AA group. Thus, a nanoplate-like HA coating has good potential in improving the osteoinductivity and osteogenic activity of porous Ti implants in clinical applications.
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http://dx.doi.org/10.1039/d0nr06306aDOI Listing
December 2020

The Activity and Safety of Anlotinib for Patients with Extremity Desmoid Fibromatosis: A Retrospective Study in a Single Institution.

Drug Des Devel Ther 2020 25;14:3941-3950. Epub 2020 Sep 25.

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.

Purpose: Desmoid fibromatosis (DF) is an aggressive fibroblastic neoplasm with a high propensity for local recurrence. Although multiple therapeutic modalities seem effective for DF, the standard systemic treatment for symptomatic and progressive DF remains controversial. As targeted therapy, tyrosine kinase inhibitors have been recently reported to contribute to the treatment of DF. Thus, the purpose of this study was to assess the efficacy and safety of anlotinib, a novel multi-kinase angiogenesis inhibitor, in patients with DF.

Patients And Methods: We retrospectively collected the clinical medical records of patients with extremity DF who received anlotinib between January 2019 and January 2020 in our center. Anlotinib was started with a dose of 8 mg daily and adjusted according to the drug-related toxicity. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors 1.1 criteria. Progression-free survival (PFS) was identified as the primary endpoint and analyzed using the Kaplan-Meier method.

Results: In total, 21 (6 male, 15 female) consecutive patients with DF were enrolled. The median medication time was nine months (Q1, Q3: 7.5, 10.5). None of the patients achieved a complete response, but eight (38.1%) patients achieved a partial response and ten patients (47.6%) achieved disease stability. Three (14%) patients developed progressive disease and the 3-, 6-, and 12-month PFS rates were 95.2%, 90.5%, and 84.0%, respectively. The disease control rate was 86.0% (18/21) and the objective response rate was 38.1% (8/21). Moreover, 15/21 (71.4%) patients achieved a reduction in tumor size, accompanied with a decrease in T2-weighted signal intensity on magnetic resonance imaging and clinical benefit.

Conclusion: Anlotinib was effective against DF with an acceptable safety profile, and significantly slowed the disease progression. Further, multicenter studies with a longer follow-up time are needed to characterize fully the clinical application of anlotinib in DF.
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http://dx.doi.org/10.2147/DDDT.S271008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524188PMC
September 2020

Electrochemical Deposition of Nanostructured Hydroxyapatite Coating on Titanium with Enhanced Early Stage Osteogenic Activity and Osseointegration.

Int J Nanomedicine 2020 8;15:6605-6618. Epub 2020 Sep 8.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, People's Republic of China.

Purpose: The aim of research is to fabricate nanostructured hydroxyapatite (HA) coatings on the titanium via electrochemical deposition (ED). Additionally, the biological properties of the ED-produced HA (EDHA) coatings with a plate-like nanostructure were evaluated in vitro and in vivo by undertaking comparisons with those prepared by acid/alkali (AA) treatment and by plasma spray-produced HA (PSHA) nanotopography-free coatings.

Materials And Methods: Nanoplate-like HA coatings were prepared through ED, and nanotopography-free PSHA coatings were fabricated. The surface morphology, phase composition, roughness, and wettability of these samples were investigated. Furthermore, the growth, proliferation, and osteogenic differentiation of MC3T3-E1 cells cultured on each sample were evaluated via in vitro experiments. Histological assessment and push-out tests for the bone-implant interface were performed to explore the effect of the EDHA coatings on the interfacial osseointegration in vivo.

Results: XRD analysis showed that the strongest intensity for the EDHA coatings was at the (002) plane rather than at the regular (211) plane. Relatively higher surface roughness and greater wettability were observed for the EDHA coatings. Cellular experiments revealed that the plate-like nanostructured EDHA coatings not only possessed an ability, similar to that of PSHA coatings, to promote the adhesion and proliferation of MC3T3-E1 cells but also demonstrated significantly enhanced early or intermediate markers of osteogenic differentiation. Significant osseointegration enhancement in the early stage of implantation period and great bonding strength were observed at the interface of bone and EDHA samples. In comparison, relatively weak osseointegration and bonding strength of the bone-implant interface were observed for the AA treatment.

Conclusion: The biological performance of the plate-like nanostructured EDHA coating, which was comparable with that of the PSHA, improves early-stage osteogenic differentiation and osseointegration abilities and has great potential for enhancing the initial stability and long-term survival of uncemented or 3D porous titanium implants.
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http://dx.doi.org/10.2147/IJN.S268372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490093PMC
December 2020

PTEN in osteosarcoma: Recent advances and the therapeutic potential.

Biochim Biophys Acta Rev Cancer 2020 12 19;1874(2):188405. Epub 2020 Aug 19.

Department of Orthopedics, West China Hospital, Sichuan University, Guoxue Xiang No. 37, Chengdu, Sichuan 610041, People's Republic of China. Electronic address:

Osteosarcoma is the most common primary malignant bone tumor, predominantly occurring in children and adolescents. Despite treated with surgery and neoadjuvant chemotherapy, osteosarcoma has a high potential of local recurrence and lung metastasis. Overall survival rates for osteosarcoma have plateaued in the past four decades, therefore, identification of novel targets and development of more effective treatment strategies are urgent. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene that negatively regulates the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway. Over half of clinical osteosarcoma samples presented loss or low expression of PTEN, which usually indicated an advanced stage of tumor and a poor prognosis. The expression of PTEN is regulated by epigenetic silence, transcription regulation, post-translational modifications, and protein interactions in osteosarcoma. Therefore, explicating regulations to restore the anti-tumor function of PTEN might provide novel targeted therapies for osteosarcoma. Preclinical evidence suggested directly targeting the altered PTEN in osteosarcoma was promising. Current clinical application of PTEN related therapies in osteosarcoma are PI3K/mTOR inhibitors, and these drugs have shown the favorable efficacy in patients with advanced osteosarcoma.
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http://dx.doi.org/10.1016/j.bbcan.2020.188405DOI Listing
December 2020

Clinical Guideline for Microwave Ablation of Bone Tumors in Extremities.

Orthop Surg 2020 Aug 9;12(4):1036-1044. Epub 2020 Aug 9.

Department of Orthopedics, Guiqian International General Hospital, Guiyang, China.

Microwave ablation has been used to treat bone tumors in extremities for more than 30 years. With improved recognition, updated microwave equipment, and expanded clinical application, microwave ablation has recently been widely used to treat bone tumors. To standardize the application of microwave ablation in the clinical treatment of bone tumors in the limbs, research results and clinical experience involving the use of microwave ablation to treat bone tumors in the limbs have been summarized, and a clinical guideline has been designed. This guideline is aimed at providing a reliable clinical basis for indications, preoperative evaluation and decision-making, perioperative treatment, complications, and other issues via evidence-based medicine. Two aspects are considered-percutaneous microwave ablation and intraoperative microwave ablation of bone tumors in extremities. Ultimately, the guideline is intended to standardize treatment and improve the clinical efficacy of microwave ablation of bone tumors in extremities.
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http://dx.doi.org/10.1111/os.12749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454210PMC
August 2020

The Efficacy and Safety of Apatinib in Advanced Synovial Sarcoma: A Case Series of Twenty-One Patients in One Single Institution.

Cancer Manag Res 2020 1;12:5255-5264. Epub 2020 Jul 1.

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People's Republic of China.

Background: Synovial sarcoma (SS) is a highly aggressive soft-tissue sarcoma (STS) with poor prognosis. Tyrosine kinase inhibitor (TKI) has shown a promising impact on advanced STS patients. This study aimed to evaluate the efficacy and safety of apatinib, an oral multi-TKI, which especially inhibited vascular endothelial growth factor receptor, as second-line therapy for patients with advanced SS.

Patients And Methods: This retrospective analysis included 21 advanced SS patients, who had a poor response to anthracycline-based chemotherapy alone or combined with ifosfamide at least one cycle. All the patients received an apatinib containing regimen between May 2016 and October 2019 in our institution. Apatinib 500-750 mg (250 mg for patients younger than 10) was given daily. Tumor responses were assessed by response evaluation criteria in solid tumors. Survival analysis was performed by the Kaplan-Meier test, and a safety profile was recorded.

Results: The median follow-up was 15.2 months (95% CI, 12.2-NE). Nine (42.9%) patients had partial response (PR), and eight (38.1%) had stable disease. The median progression-free survival (PFS) was 13.1 months (95% CI, 6.7-NE). The 6- and 12-month PFS rates were 76.2% (95% CI, 60.0-96.8) and 55.4% (95% CI, 37.3-82.3), respectively. Additionally, the median overall survival (OS) was 15.5 months (95% CI, 10.7-NE). The 6- and 12-month OS rates were 81.0% (95% CI, 65.8, 99.6) and 64.9% (95% CI, 46.9-90.0), respectively. Moreover, the objective response rate was 42.9% (9/21) for advanced SS patients. The disease control rate was 81.0% (17/21). For the nine patients with the best response of PR, the median duration of response was 7.7 months.

Conclusion: Apatinib was proved to be a potential second-line treatment option for advanced SS patients with chemo-resistance. Apatinib showed promising efficacy and acceptable safety profile in advanced SS, with considerable OS and particularly PFS. Indeed, further multicenter studies with a longer follow-up time are needed to fully determine the clinical application of apatinib in advanced SS.
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http://dx.doi.org/10.2147/CMAR.S254296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335867PMC
July 2020

Three-dimensional-printed customized prosthesis for pubic defect: prosthesis design and surgical techniques.

J Orthop Surg Res 2020 Jul 13;15(1):261. Epub 2020 Jul 13.

Department of Orthopedics, West China Hospital, Sichuan University, No. 37 Guoxuexiang, Chengdu, 610041, Sichuan, People's Republic of China.

Background: This study is to describe the detailed design and surgical techniques of three-dimensional (3D)-printed customized prosthesis for pubic bone defect.

Patients And Methods: Five patients under type III resections were included in this study. Based on radiography data, 3D pelvic model was established and virtual surgery was simulated. Detailed anatomy data were measured including the size and arc of normal pubis, the size of residual bone in acetabular side. Different fixation ways were considered according to shape of defect. After features modification and porous structure design, prostheses were fabricated. The osteotomy guides and plastic models were used during surgery.

Result: Of 5 cases, the prostheses consist of the type with stem (3, 60%) and the type without stem (2, 40%). Mean follow-up period was 13.6 months (range, 8-24 months). For partial pubis removed cases, the mean length and width of narrowest part of normal superior pubis were 13.19 mm (range, 12.51-14.12 mm) and 7.80 mm (range, 7.18-8.26 mm) respectively. Mean arc of normal pubis was 2.71 rad (range, 2.66-2.73 rad). For the entire pubis resection cases, the mean diameter of narrowest parts and length of normal superior pubis were 11.52 mm (range, 11.13-11.91 mm) and 64.78 mm (range, 63.46-66.09 mm), while the diameter of narrowest part and length of normal inferior pubis were 7.37 mm (range, 7.20-7.54 mm) and 86.43 mm (range, 84.28-88.57 mm). Mean length and arc of intramedullary stem was 20 mm (range, 18-21 mm) and 2.7 rad. Mean screw holes number was 6.3 (range, 6-7) while ultimate screws number in surgeries was 4.3 (range, 4-5). Porous structure with 600-μm-pore size and 70% porosity was applied in parts of contact with residual bone.

Conclusion: 3D-printed customized prostheses could be a feasible option to reconstruct bone defect after type III resection. The design of 3D-printed customized prostheses is a multi-step process which is based on strict anatomic measurement.
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http://dx.doi.org/10.1186/s13018-020-01766-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7359288PMC
July 2020

Effects of Nanotopography Regulation and Silicon Doping on Angiogenic and Osteogenic Activities of Hydroxyapatite Coating on Titanium Implant.

Int J Nanomedicine 2020 12;15:4171-4189. Epub 2020 Jun 12.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China.

Background: Angiogenic and osteogenic activities are two major problems with biomedical titanium (Ti) and other orthopedic implants used to repair large bone defects.

Purpose: The aim of this study is to prepare hydroxyapatite (HA) coatings on the surface of Ti by using electrochemical deposition (ED), and to evaluate the effects of nanotopography and silicon (Si) doping on the angiogenic and osteogenic activities of the coating in vitro.

Materials And Methods: HA coating and Si-doped HA (HS) coatings with varying nanotopographies were fabricated using two ED modes, ie, the pulsive current (PC) and cyclic voltammetry (CV) methods. The coatings were characterized through scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), and atomic force microscopy (AFM), and their in vitro bioactivity and protein adsorption were assessed. Using MC3T3-E1 pre-osteoblasts and HUVECs as cell models, the osteogenic and angiogenic capabilities of the coatings were evaluated through in vitro cellular experiments.

Results: By controlling Si content in ~0.8 wt.%, the coatings resulting from the PC mode (HA-PC and HS-PC) and CV mode (HA-CV and HS-CV) had nanosheet and nanorod topographies, respectively. At lower crystallinity, higher ionic dissolution, smaller contact angle, higher surface roughness, and more negative zeta potential, the HS and PC samples exhibited quicker apatite deposition and higher BSA adsorption capacity. The in vitro cell study showed that Si doping was more favorable for enhancing the viability of the MC3T3-E1 cells, but nanosheet coating increased the area for cell spreading. Of the four coatings, HS-PC with Si doping and nanosheet topography exhibited the best effect in terms of up-regulating the expressions of the osteogenic genes (ALP, Col-I, OSX, OPN and OCN) in the MC3T3-E1 cells. Moreover, all leach liquors of the surface-coated Ti disks promoted the growth of the HUVECs, and the HS samples played a more significant role in promoting cell migration and tube formation than the HA samples. Of the four leach liquors, only the two HS samples up-regulated NO content and expressions of the angiogenesis-related genes (VEGF, bFGF and eNOS) in the HUVECs, and the HS-PC yielded a better effect.

Conclusion: The results show that Si doping while regulating the topography of the coating can help enhance the bone regeneration and vascularization of HA-coated Ti implants.
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http://dx.doi.org/10.2147/IJN.S252936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297339PMC
August 2020

[Long-term effectiveness of "West China Classification" guided surgical treatment of desmoid-type fibromatosis in shoulder girdle].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2020 Jun;34(6):744-750

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China.

Objective: To evaluate the long-term effectiveness of patients received surgical treatment under the guidance of "West China Classification" of desmoid-type fibromatosis (DTF) in the shoulder girdle.

Methods: The clinical data of 32 patients with DTF in the shoulder girdle admitted between June 2003 and December 2016 were retrospectively analyzed, including 14 males and 18 females, aged 14-56 years with an average age of 36.8 years. The maximum diameter of the tumor was 7-19 cm, with an average of 11.1 cm. According to the "West China Classification" of DTF in the shoulder girdle, there were 4 cases of region Ⅰ, 3 cases of region Ⅱ, 6 cases of region Ⅲ, 3 cases of region Ⅳ, 5 cases of regions Ⅰ+Ⅱ, 5 cases of regions Ⅱ+Ⅲ, and 6 cases of regions Ⅰ+Ⅱ+Ⅲ. In addition, the involvement of blood vessels and nerves was also taken into consideration for choosing a surgical approach. Finally, 12 cases were operated via anteroposterior approach (group A), 14 via posterior approach (group B), and 6 via combined anterior-posterior approach (group C). The 1993 Musculoskeletal Tumor Society (MSTS93) score (including pain, limb function, satisfaction, hand position, hand flexibility, and lifting ability), Japanese Orthopedic Association (JOA) score, range of motion (ROM) of shoulder joint (including flexion, extension, abduction, and adduction), and complications of patients in the 3 groups were recorded and compared.

Results: All the 32 patients were followed up 30-190 months, with an average of 94.6 months. At last follow-up, complications occurred in 5 cases (15.6%), including 2 cases (16.6%) in group A, 2 (14.3%) in group B, and 1 (16.6%) in group C. There was no significant difference in the incidence of complications among the 3 groups ( =1.000). Tumor recurrence occurred in 5 (15.6%) cases, including 1 (8.3%) case in group A, 2 (14.3%) in group B, and 1 (16.6%) in group C. No significant difference was found in the recurrence rate among the 3 groups ( =1.000). At last follow-up, MSTS93 score of pain, limb function, satisfaction, hand flexibility, and hand position in groups A and B were significantly better than those in group C ( <0.05), even though no significant difference existed between group A and group B ( >0.05). The lifting ability score in group C was significantly lower than in group A ( <0.05), and no significant difference was found between other groups ( >0.05). The JOA score and flexion, extension, abduction, and adduction activities of shoulder in groups A and B were significantly better than those in group C ( <0.05). The extension activity in group A was significantly better than that in group B ( <0.05), the flexion activity in group B was significantly better than that in group A ( <0.05). There was no significant difference in other indexes between groups A and B ( >0.05).

Conclusion: Taking a rational approach to fully expose and completely remove the tumor is the key point of surgical treatment for patients with DTF in the shoulder girdle. At the same time, preservation of vital structures and reconstruction of soft tissues should also be taken into consideration. Overall, surgical treatment under the guidance of "West China Classification" of DTF in the shoulder girdle has achieved satisfactory long-term effectiveness.
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http://dx.doi.org/10.7507/1002-1892.201912143DOI Listing
June 2020

Surgical trauma-induced immunosuppression in cancer: Recent advances and the potential therapies.

Clin Transl Med 2020 Jan;10(1):199-223

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Surgical resection remains the mainstay treatment for solid cancers, especially for localized disease. However, the postoperative immunosuppression provides a window for cancer cell proliferation and awakening dormant cancer cells, leading to rapid recurrences or metastases. This immunosuppressive status after surgery is associated with the severity of surgical trauma since immunosuppression induced by minimally invasive surgery is less than that of an extensive open surgery. The systemic response to tissue damages caused by surgical operations and the subsequent wound healing induced a cascade alteration in cellular immunity. After surgery, patients have a high level of circulating damage-associated molecular patterns (DAMPs), triggering a local and systemic inflammation. The inflammatory metrics in the immediate postoperative period was associated with the prognosis of cancer patients. Neutrophils provide the first response to surgical trauma, and the production of neutrophil extracellular traps (NETs) promotes cancer progression. Activated macrophage during wound healing presents a tumor-associated phenotype that cancers can exploit for their survival advantage. In addition, the amplification and activation of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) or the elevated programmed death ligand-1 and vascular endothelial growth factor expression under surgical trauma, exacerbate the immunosuppression and favor of the formation of the premetastatic niche. Therapeutic strategies to reduce the cellular immunity impairment after surgery include anti-DAMPs, anti-postoperative inflammation or inflammatory/pyroptosis signal, combined immunotherapy with surgery, antiangiogenesis and targeted therapies for neutrophils, macrophages, MDSCs, and Tregs. Further, the application of enhanced recovery after surgery also has a feasible outcome for postoperative immunity restoration. Overall, current therapies to improve the cellular immunity under the special condition after surgery are relatively lacking. Further understanding the underlying mechanisms of surgical trauma-related immunity dysfunction, phenotyping the immunosuppressive cells, and developing the related therapeutic intervention should be explored.
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http://dx.doi.org/10.1002/ctm2.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240866PMC
January 2020

What are the Complications of Three-dimensionally Printed, Custom-made, Integrative Hemipelvic Endoprostheses in Patients with Primary Malignancies Involving the Acetabulum, and What is the Function of These Patients?

Clin Orthop Relat Res 2020 Nov;478(11):2487-2501

J. Wang, L. Min, M. Lu, Y. Zhang, Y. Wang, Y. Luo, Y. Zhou, H. Duan, C. Tu, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Background: Functional reconstruction after resection of pelvic malignancies involving the acetabulum remains challenging. Numerous reconstruction methods have been proposed, but they are generally associated with mechanical and nonmechanical complications. To improve the function of patients with primary malignancies of the acetabulum after internal hemipelvectomy and reduce the complication rate after this procedure, we designed a series of three-dimensionally (3D) printed, custom-made, integrative hemipelvic endoprostheses with a porous structure and wanted to present the early results of using this construct to determine whether it could be considered a reasonable reconstruction option.

Questions/purposes: We performed this study to (1) evaluate, in a small group of patients, whether the new endoprosthesis restores short-term lower-limb function; (2) identify short-term complications associated with the use of this endoprosthesis; and (3) assess osseointegration between the host bone and the 3D-printed integrative hemipelvic endoprosthesis with a porous structure.

Methods: Between October 2016 and May 2017, our center treated 26 patients with malignancies involving the acetabulum. Thirteen of these patients received hemipelvic replacement with a 3D-printed, custom-made, integrative endoprosthesis, six received hemipelvic replacement with a modular endoprosthesis, four received radiotherapy, and three received external hemipelvectomy. Resection and reconstruction with a 3D-printed, custom-made, integrative endoprosthesis were indicated if the resection margin was the same as that achieved in hemipelvectomy, if reconstruction would preserve reasonable function after resection, if the patient had a good physical status and life expectancy longer than 6 months, and if the patient was willing to accept the potential risk of a 3D-printed, custom-made, endoprosthesis. The exclusion criteria were an inability to achieve a satisfactory surgical margin with limb salvage, inability to preserve the function of the limb because of tumor involvement of the sacral nerve or sciatic nerve, and unresectable and/or widely metastatic disease on presentation. Pain and function were evaluated with the 10-cm VAS score (range 0 to 10; a lower score is desirable), the 1993 version of the Musculoskeletal Tumor Society (MSTS-93) score (range 0 to 30; a higher score is desirable), and the Harris hip score ([HHS]; range 0 to 100; a higher score is desirable) were evaluated preoperatively and at a median of 27 months after reconstruction (range 24 to 31 months). The functional scores and complications were recorded after reviewing the patients' records. Osseointegration was assessed with digital tomosynthesis by two senior surgeons. We observed the trabecular structures connected to the implant surface to assess whether there was good osseointegration.

Results: The median preoperative VAS score, MSTS-93 score, and HHS were 5 (range 2 to 8), 14 (range 3 to 18), and 64 (range 20 to 76) points, respectively. At the latest follow-up interval, the median VAS score, MSTS-93 score, and HHS were 2 (range 0 to 6), 23 (range 15 to 27), and 82 (range 44 to 93) points, respectively. No deep infection, dislocation, endoprosthetic breakage, aseptic loosening, or local recurrence occurred. Two patients experienced delayed wound healing; the wounds healed after débridement. Using digital tomography, we found that all implants were well-osseointegrated at the final follow-up examination.

Conclusions: A 3D-printed, custom-made, integrative hemipelvic endoprosthesis provides acceptable early outcomes in patients undergoing pelvic reconstruction. Osseointegration is possible, and we anticipate this will lead to biologic stability with a longer follow-up interval. The custom-made integrative design ensured precise implantation. Although a few patients in this study had only a short follow-up duration, the functional results were reasonable. We have observed no major complications so far, but this was a very small series and we caution that these are large reconstructions that will certainly result in complications for some patients. Our method uses a precise preoperative simulation and endoprosthesis design to aid the surgeon in performing challenging operations. If our early results are confirmed with more patients and longer follow-up and are replicated at other centers, this may be a reconstruction option for patients with periacetabular malignancies.

Level Of Evidence: Level IV, therapeutic study.
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http://dx.doi.org/10.1097/CORR.0000000000001297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594920PMC
November 2020

Intercalary Reconstruction of the "Ultra-Critical Sized Bone Defect" by 3D-Printed Porous Prosthesis After Resection of Tibial Malignant Tumor.

Cancer Manag Res 2020 8;12:2503-2512. Epub 2020 Apr 8.

Department of Orthopeadics, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.

Purpose: This study aimed to evaluate the early stability, limb function, and mechanical complications of 3D-printed porous prosthetic reconstruction for "ultra-critical sized bone defects" following intercalary tibial tumor resections.

Methods: This study defined an "ultra-critical sized bone defect" in the tibia when the length of segmental defect in the tibia was >15.0 cm or >60% of the full tibia and the length of the residual fragment in proximal or distal tibia was between 0.5 cm and 4.0 cm. Thus, five patients with "ultra-critical sized bone defects" following an intercalary tibial malignant tumor resection treated with 3D-printed porous prosthesis between June 2014 and June 2018 were retrospectively reviewed. Patient information, implants design and fabrication, surgical procedures, and early clinical outcome data were collected and evaluated.

Results: Among the five patients, three were male and two were female, with an average age of 30.2 years. Pathological diagnoses were two osteosarcomas, one Ewing sarcoma, one pseudo-myogenic hemangioendothelioma, and one undifferentiated pleomorphic sarcoma . The average length of the bone defects following tumor resection was 22.8cm, and the average length of ultra-short residual bone was 2.65cm (range=0.6cm-3.8cm). The mean follow-up time was 27.6 months (range=14.0-62.0 months). Early biological fixation was achieved in all five patients. The average time of clinical osseointegration at the bone-porous interface was 3.2 months. All patients were reported to be pain free and have no limitations in their walking distance. No prosthetic mechanical complications were observed.

Conclusion: Reconstruction of the "ultra-critical sized bone defect" after an intercalary tibial tumor resection using 3D-printed porous prosthesis achieved satisfactory overall early biological fixation and limb function. Excellent primary stability and the following rigid biological fixation were key factors for success. The outcomes of this study were supposed to support further clinical application and evaluation of 3D-printed porous prosthetic reconstruction for "ultra-critical sized bone defects" in the tibia.
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http://dx.doi.org/10.2147/CMAR.S245949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152541PMC
April 2020

The functional outcomes and complications of different reconstruction methods for Giant cell tumor of the distal radius: comparison of Osteoarticular allograft and three-dimensional-printed prosthesis.

BMC Musculoskelet Disord 2020 Feb 3;21(1):69. Epub 2020 Feb 3.

Department of Orthopedics, West China Hospital, Sichuan University, No. 37 Guoxuexiang, Chengdu, 610041, Sichuan, People's Republic of China.

Background: En bloc excision has been increasingly used for the management of giant cell tumors (GCTs) in the distal radius. An osteoarticular allograft has been used extensively for decades, and custom-made prosthesis reconstruction has been more recently applied. We aimed to compare the clinical outcomes of the two procedures.

Methods: We retrospectively analyzed 30 patients with Campanacci III or recurrent GCTs of the distal radius for follow-up at a mean of 33.2 months. In total, 15 underwent osteoarticular allograft reconstruction (allograft group) and 15 received cementless three-dimensional (3D)-printed prosthesis reconstruction (prosthesis group) between March 18, 2013, and May 20, 2018. All patients underwent by clinical and radiological examinations, including pre- and postoperative active range of motion (ROM) of the wrist, VAS score, grip strength, degenerative change of wrist, Mayo wrist score and Musculoskeletal Tumor Society (MSTS) score. Complications were evaluated using the Henderson classification.

Results: Both groups showed significantly increased ROM, grip strength, Mayo score and MSTS score postoperatively. Furthermore, the extension, flexion, MSTS, and Mayo score were significantly higher in the prosthesis group. There was no significant difference in grip strength and VAS between the groups. In allograft group, one patient had a late infection one had resorption of allograft without allograft bone fracture. and four had wrist subluxation. All patients had degenerative changes (mean 9 months). In the prosthesis group, three patients developed wrist subluxation, three had separation of the distal radioulnar joint, and none of the patients developed wrist degeneration.

Conclusions: Our study compared the objective functional outcomes and complications of two reconstructive methods for Campanacci III or recurrent GCT in the distal radius. 3D-printed prosthesis replacement can partially preserve wrist function better than allograft reconstruction in the short-term. During the design of 3D-printed prosthesis, preoperative morphological assessment of the affected proximal row carpal is helpful to control postoperative dislocation. After allograft reconstruction, wrist degeneration, which has been demonstrated in all patients, severely influence their wrist function. Therefore, compared to allograft reconstruction, 3D-printed prosthesis reconstruction has irreplaceable advantages at early-stage application, especially in wrist function, however, further studied with a larger number of cases and longer follow-up.
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http://dx.doi.org/10.1186/s12891-020-3084-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6998256PMC
February 2020

Gorham-Stout disease of the malleolus: a rare case report.

BMC Musculoskelet Disord 2019 Dec 31;21(1). Epub 2019 Dec 31.

Department of Joint and Musculoskeletal Tumor, The First Affiliated Hospital of Shenzhen University, Sungang west road No. 3002, Shenzhen, Guangdong, 518000, People's Republic of China.

Background: Gorham-Stout disease, also known as vanishing bone disease, idiopathic massive osteolysis, is a rare entity of unknown etiopathology. This disease is characterized by destruction of osseous matrix and proliferation of lymphatic vascular structures and associated with massive regional osteolysis. It has a variable clinical presentation and is commonly considered as a benign disease with a progressive tendency and an unpredictable prognosis. The diagnosis is made by exclusion and based on combination with histological, radiological, and clinical features. Despite that several therapeutic options have shown certain efficacy, the effective treatment still remains controversial and there is no standard treatment to be recommended.

Case Presentation: A previously healthy 40-year-old man presented with right lateral malleolus pain after an ankle sprain and was referred to our hospital. The radiographs indicated rapid massive bone destruction in the distal right lateral malleolus with an unclear margin. Based on the combination with histological, radiological, and clinical features, the diagnosis of Gorham-Stout disease was made. Considering that the residual function of malleolus had to be protected, prior bisphosphonate was used to control the progression of lesion, followed by surgical resection and biological reconstruction with autologous fibular bone grafting. The patient was followed up 8 years after surgery, he presented without progression and recurrence.

Conclusions: We depict a case of Gorham-Stout disease at the right lateral malleolus and was successfully controlled by medication and surgical intervention. Based on the prior effective medical treatment, resection with biological reconstruction is a useful approach to treat Graham-Stout disease in bone.
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http://dx.doi.org/10.1186/s12891-019-3027-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937978PMC
December 2019

Three-dimensional-printed custom-made hemipelvic endoprosthesis for primary malignancies involving acetabulum: the design solution and surgical techniques.

J Orthop Surg Res 2019 Nov 27;14(1):389. Epub 2019 Nov 27.

Department of Orthopedics, West China Hospital, Sichuan University, No. 37 Guoxuexiang, Chengdu, 610041, Sichuan, People's Republic of China.

Background: This study is to describe the detailed design and surgical techniques of three-dimensional (3D)-printed custom-made endoprosthesis for hemipelvic tumorous bone defect.

Methods: According to the pelvic tumor resection classification by Enneking and Dunham, the hemipelvis is divided into three zones including the ilium (P1), acetabulum (P2), and pubis and ischium (P3). Thirteen patients were included in this study. Of these, P1 and P2 were involved in three cases, while P1, P2, and P3 were involved in 10. Based on radiography data, 3D pelvic model was rebuilt, and virtual surgery was simulated. Different fixation methods were applied according to residual bone volume. Parameters of the first sacral (S) vestibule, second sacral (S) vestibule, the narrowest zone of superior pubic medullary cavity (NPSPMC), and the resected surface of superior pubic medullary cavity (RSSPMC) were selectively measured in various fixation methods. Model overlapping, feature simplifying, and size controlling were three basic steps during design procedure. Volume proportion of porous structure was determined according to estimated weight of resected specimen. Acetabular location, anteversion, and inclination were modulated. Screw diameter, direction, and combination were considered. The osteotomy guides and plastic models were used during surgery.

Results: Of 13 cases, after P1 resection, endoprostheses were fixed to sacra (8; 61.5%), ilia (3; 23.1%), and both (2; 15.4%). After P3 resection, endoprostheses were fixed to residual acetabulum (3; 23.1%), and residual pubis by stem (8; 61.5%) or "cap-like" structure (2; 15.4%). Mean area of the S vestibule, S vestibule, RSSPMC, and PSPMC were 327.9 (222.2 to 400), 131.7 (102.6 to 163.6), 200.5 (103.8 to 333.2), and 79.8 mm (40.4 to 126.2), respectively. Porous structure with 600 μm pore size and 70% porosity accounted for 68.8% (53.0 to 86.0) of the whole endoprosthesis on average. Mean acetabular anteversion and inclination were designed as 23.2° (20 to 25) and 42.4° (40 to 45). Median numbers of screws designed in the S vestibule was 5 (IQR, 4 to 6), in the S2 vestibule was 1 (IQR, 1 to 2), in the ilium was 5 (IQR, 2 to 6), and in the pubis was 1 (IQR, 1 to 1), while screws designed in the ischium was all 2. Median number of screws inserted in the S vestibule was 4 (IQR, 3 to 4), in the S vestibule was 1 (IQR, 1 to 1), in the ilium was 3 (IQR, 1 to 5), in the pubis was 1 (IQR, 0 to 1), and in the ischium was 1 (IQR, 1 to 1).

Conclusions: This study firstly presents detailed design and related surgical techniques of 3D-printed custom-made hemipelvic endoprosthesis reconstruction. Osseointegration is critical for long-term outcome and requires three design elements including interface connection, porous structure, and initial stability achieved by precise matching and proper fixation methods.
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http://dx.doi.org/10.1186/s13018-019-1455-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882053PMC
November 2019